Interstitial nephritis, an important kidney disease in its own right, is also a predicable sequelae of many forms of progressive glomerulonephritis. As a cause of renal injury it affects large numbers of people in this country and is a major contributor to the process of chronic renal failure. Present evidence suggests the direct participation of several immunologic effector mechanisms in the pathogenesis of interstitial nephritis. These processes whic inclulde antibody deposition, cell-mediated cytotoxicity, and delayed hypersensitivity are probably modulated by genetic constraints collaborating with humoral and cell-mediated regulatory influences which follow rules formulated in present-day network theories of immunologic science. The basic theme of this research proposal is to further characterize the pathogenesis of disease activation and immune regulation in an experimental model of anti-tubular basement membrane disease producing interstitial nephritis in inbred rats. These studies will cloely examine the role of genetically-defined immune respones, T lymphocytes subpopulations, and idiotypic influence on the control of disease. Our investigations will take advantage of standard and recombinant rat strains which differentially express disease, hybridoma-producing monoclonal anti-tubular basement membrane antibodies, in vitro assays of antibody synthesis and delayed hypersensitivity, and recently defined antisera which can separate rat T lymphocytes into subpopulations. Specific studies will assess regulatory collaborations controlling effector events as well as the modulation of self-tolerance. Following this acquisition of basic information, methods of manipulating these immune events will be developed so as to derive a rational basis for immunoprophylaxis or selected immunotherapy. Attempts to favorably alter the natural history of developing interstital nephritis by antiidiotypic modulation will be specifically pursued. Studies such as these should ultimately provide an appropriate experimental framework for approaching similar problems in human kidney disease.